The overall objective of this research program is to continue our efforts directed at the development of efficient procedures for the construction of the eremantholides (A,B and C), jatropholone A and B, and related natural products which appear to have significant potential as antitumor agents. As new synthetic targets in this area we have chosen echinosporin and the hydroxyjatrophones (A, B and C). The latter were isolated and their structures elucidated in our laboratory. Concommitant with the development of our approach to these targets, we will: (A) Explore the synthetic utility of the TiCl4 catalyzed intramolecular crossed aldol condensation for construction of medium and large rings; (B) Define the scope and limitations of the intramolecular [2+2]-photocycloaddition of enones and butenolides to acetylenic moieties. Included here will be a study of the stereochemical consequences of such cycloadditions, and (C) Explore the novel reductive cyclization of acetylenic ketones induced by chromium (II)-sulfate. In addition to the above quite specific synthetic goals, a more general underlying and long range aim of this research program is the development of a better understanding of the molecular architecture responsible for the antitumor properties of these and related systems. Thus, as we develop our method of procedure for each of the above synthetic targets, we will also introduce various model systems which will be amenable to construction and subsequent testing, such that in the end we will be able to dissect out the critical structural feature or features responsible for the observed antitumor properties. Once such features are identified, the design of new and possibly more effective antitumor drugs should be feasible. In this regard five compounds emanating from this research program demonstrated significant antitumor activity.